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Article ; Online: Identifying the potential origin of mucin in primary cutaneous mucinoses-A retrospective study and analysis using histopathology and multiplex fluorescence staining.

Steinmann, S / Guillet, C / Cheng, P F / Levesque, M P / Dummer, R / Kolm, I / Maul, J T

Journal of the European Academy of Dermatology and Venereology : JEADV

2023 Volume 37, Issue 7, Page(s) 1302–1310

Abstract: Background: Primary cutaneous mucinoses (PCM) are rare diseases characterized by dermal or follicular mucin deposits.: Objectives: A retrospective study characterizing PCM to compare dermal with follicular mucin to identify its potential origin on a ... ...

Abstract	Background: Primary cutaneous mucinoses (PCM) are rare diseases characterized by dermal or follicular mucin deposits. Objectives: A retrospective study characterizing PCM to compare dermal with follicular mucin to identify its potential origin on a single-cell level. Material and methods: Patients diagnosed with PCM between 2010 and 2020 at our department were included in this study. Biopsy specimens were stained using conventional mucin stains (Alcian blue, PAS) and MUC1 immunohistochemical staining. Multiplex fluorescence staining (MFS) was used to investigate which cells were associated with MUC1 expression in select cases. Results: Thirty-one patients with PCM were included, 14 with follicular mucinosis (FM), 8 with reticular erythematous mucinosis, 2 with scleredema, 6 with pretibial myxedema and one patient with lichen myxedematosus. In all 31 specimens, mucin stained positive for Alcian blue and negative for PAS. In FM, mucin deposition was exclusively found in hair follicles and sebaceous glands. None of the other entities showed mucin deposits in follicular epithelial structures. Using MFS, all cases showed CD4+ and CD8+ T cells, tissue histiocytes, fibroblasts and pan-cytokeratin+ cells. These cells expressed MUC1 at different intensities. MUC1 expression in tissue histiocytes, fibroblasts, CD4+ and CD8+ T cells, and follicular epithelial cells of FM was significantly higher than the same cell types in the dermal mucinoses (p < 0.001). CD8+ T cells were significantly more involved in expression of MUC1 than all other analysed cell types in FM. This finding was also significant in comparison with dermal mucinoses. Conclusion: Various cell types seem to contribute to mucin production in PCM. Using MFS, we showed that CD8+ T cells seem to be more involved in the production of mucin in FM than in dermal mucinoses, which could indicate that mucin in dermal and follicular epithelial mucinoses have different origins.
MeSH term(s)	Humans ; Mucinoses/diagnosis ; Mucinoses/metabolism ; Mucinoses/pathology ; Mucins/metabolism ; Retrospective Studies ; Alcian Blue ; Scleromyxedema ; Staining and Labeling
Chemical Substances	Mucins ; Alcian Blue (P4448TJR7J)
Language	English
Publishing date	2023-03-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1128828-0
ISSN	1468-3083 ; 0926-9959
ISSN (online)	1468-3083
ISSN	0926-9959
DOI	10.1111/jdv.18992
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Zs.A 3492: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 413: Show issues

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Article ; Online: Health-related quality of life in survivors of advanced melanoma treated with anti-PD1-based immune checkpoint inhibitors.

Looman, E L / Cheng, P F / Lai-Kwon, J / Morgan, L / Wakkee, M / Dummer, R / Dimitriou, F

Cancer medicine

2023 Volume 12, Issue 11, Page(s) 12861–12873

Abstract: Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival in advanced melanoma but are associated with immune-related adverse events (irAEs). This single center, cross-sectional survey aimed to describe the long-term symptom ... ...

Abstract	Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival in advanced melanoma but are associated with immune-related adverse events (irAEs). This single center, cross-sectional survey aimed to describe the long-term symptom burden and impact on health-related quality of life (HRQL) of advanced melanoma patients with sustained disease control following treatment with ICIs. Methods: Advanced melanoma patients (stage IIB, III or IV, AJCCv8), treated with anti-PD1-based ICIs, who were off-treatment and had at least 6 months follow-up from their last infusion with an ongoing response in the metastatic setting or no evidence of disease recurrence in the adjuvant setting. A paper-based questionnaire, consisting of the EORTC QLQ-C30, EORTC QLQ-FA12, and the PRO-CTCAE was administered. Results: Of 90 participants, 61 (68%) completed the questionnaire; 40 received single-agent anti-PD1, and 21 anti-PD1/anti-CTLA4. Thirty-three (54%) were treated in the adjuvant setting. At the time of enrolment, 31 (51%) participants had active treatment for a previous irAE. Overall, 18/61 (30%) participants reported long-term symptoms and trouble in physical and emotional functioning. Physical fatigue was common and interfered with daily activities (n = 12, 20%). In the PRO-CTCAE questionnaire, muscle ache (n = 12, 20%) and joint ache (n = 9, 15%) were commonly reported. Despite this, participants reported overall good health (6.00, range 2.00-7.00) and reasonable level of HRQL (6.00, range 3.00-7.00). Discussion: Melanoma survivors experience long-term symptoms in physical and psychosocial HRQL domains after ICI treatment. These results underline the importance to address existing gaps in survivorship care, implement these findings in clinical practice and increase awareness for long-term symptoms in these patients.
MeSH term(s)	Humans ; Immune Checkpoint Inhibitors/adverse effects ; Quality of Life ; Cross-Sectional Studies ; Neoplasm Recurrence, Local/drug therapy ; Melanoma/pathology ; Survivors
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2023-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.5967
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Article ; Online: Investigation of Ramsey spectroscopy in a lin-par-lin Ramsey coherent population trapping clock with dispersion detection.

Sun, X L / Zhang, J W / Cheng, P F / Xu, C / Zhao, L / Wang, L J

Optics express

2016 Volume 24, Issue 5, Page(s) 4532–4541

Abstract: We demonstrate that the lin-par-lin Ramsey coherent population ... ...

Abstract	We demonstrate that the lin-par-lin Ramsey coherent population trapping
Language	English
Publishing date	2016-03-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1491859-6
ISSN	1094-4087 ; 1094-4087
ISSN (online)	1094-4087
ISSN	1094-4087
DOI	10.1364/OE.24.004532
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Article ; Online: The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma.

Graf, N P / Koelblinger, P / Galliker, N / Conrad, S / Barysch, M / Mangana, J / Dummer, R / Cheng, P F / Goldinger, S M

Journal of the European Academy of Dermatology and Venereology : JEADV

2018 Volume 33, Issue 4, Page(s) 686–692

Abstract: Background: B-rapidly accelerated fibrosarcoma (BRAF) inhibitor encorafenib alone and in combination with MEK inhibitor binimetinib improves survival in BRAF-mutated melanoma patients. So far, the range of cutaneous adverse events has been characterized ...

Abstract	Background: B-rapidly accelerated fibrosarcoma (BRAF) inhibitor encorafenib alone and in combination with MEK inhibitor binimetinib improves survival in BRAF-mutated melanoma patients. So far, the range of cutaneous adverse events has been characterized only for established BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (trametinib, cobimetinib). Objective: The aim of this study was to investigate cutaneous adverse events emerging in melanoma patients treated with encorafenib and binimetinib. Methods: Patients treated with BRAF and MEK inhibitors in clinical trials at the University Hospital of Zurich were identified. Frequency and features of cutaneous adverse events as well as their management were assessed based on the prospectively collected clinical and histopathological data. The events emerging during encorafenib and/or binimetinib therapy were compared to other BRAF and MEK inhibitors at the institution and in the literature. Results: The most frequent cutaneous adverse events observed in patients treated with encorafenib alone (n = 24) were palmoplantar hyperkeratosis (54%), palmoplantar erythrodysesthesia (58%) and alopecia (46%). Drug-induced papulopustular eruptions prevailed in patients with binimetinib monotherapy (n = 25). The most frequent cutaneous adverse events in patients treated with encorafenib/binimetinib (n = 49) were palmoplantar hyperkeratosis (10%). Conclusion: Compared to data published for established BRAFi, encorafenib monotherapy showed less hyperproliferative cutaneous adverse events. In contrast, palmoplantar hyperkeratosis and palmoplantar erythrodysesthesia seem to occur more often. The combination of encorafenib and binimetinib is well tolerated and induces few cutaneous adverse events.
MeSH term(s)	Aged ; Alopecia/chemically induced ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Benzimidazoles/administration & dosage ; Benzimidazoles/adverse effects ; Carbamates/administration & dosage ; Carbamates/adverse effects ; Drug Eruptions/etiology ; Female ; Hand-Foot Syndrome/etiology ; Humans ; Keratosis/chemically induced ; Male ; Melanoma/drug therapy ; Melanoma/genetics ; Middle Aged ; Mutation ; Proto-Oncogene Proteins B-raf/genetics ; Skin Neoplasms/drug therapy ; Skin Neoplasms/genetics ; Sulfonamides/administration & dosage ; Sulfonamides/adverse effects
Chemical Substances	Benzimidazoles ; Carbamates ; Sulfonamides ; binimetinib (181R97MR71) ; encorafenib (8L7891MRB6) ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2018-12-13
Publishing country	England
Document type	Journal Article
ZDB-ID	1128828-0
ISSN	1468-3083 ; 0926-9959
ISSN (online)	1468-3083
ISSN	0926-9959
DOI	10.1111/jdv.15363
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Zs.A 3492: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 413: Show issues

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Article ; Online: Increased tumour cell PD-L1 expression, macrophage and dendritic cell infiltration characterise the tumour microenvironment of ulcerated primary melanomas.

Koelblinger, P / Emberger, M / Drach, M / Cheng, P F / Lang, R / Levesque, M P / Bauer, J W / Dummer, R

Journal of the European Academy of Dermatology and Venereology : JEADV

2018 Volume 33, Issue 4, Page(s) 667–675

Abstract: Background: Primary melanoma ulceration is an unfavourable prognostic factor included in current staging systems. Yet, the immunological and molecular alterations responsible for this adverse outcome have not been fully elucidated.: Objectives: We ... ...

Abstract	Background: Primary melanoma ulceration is an unfavourable prognostic factor included in current staging systems. Yet, the immunological and molecular alterations responsible for this adverse outcome have not been fully elucidated. Objectives: We aimed to identify immunological differences between ulcerated and non-ulcerated primary melanomas concerning both innate and adaptive immunity and to correlate these with clinical outcome. Methods: Formalin-fixed paraffin-embedded primary melanomas from 112 patients (pts) were analysed by immunohistochemistry. The expression of various markers identifying tumour-infiltrating lymphocytes, macrophages and dendritic cells was evaluated semi-quantitatively by three independent investigators. Tumour cell expression of programmed death-ligand 1 (PD-L1), transporter of antigen processing 1 and the MxA protein was also analysed. Results: Recurrence occurred in 21/56 pts (37.5%) with ulcerated vs. 14/56 pts (25.0%) with non-ulcerated tumours (P = 0.15). Tumour ulceration was associated with more frequent development of brain metastasis (17.6 vs. 3.6% of pts, P = 0.015). Immunohistochemistry showed an association of ulceration with the presence of intratumoural CD68 Conclusions: Our results confirm the adverse clinical outcome associated with primary melanoma ulceration, particularly concerning the risk of recurrence and subsequent development of brain metastases. The observed immunological differences suggest a conceivable role of increased intratumoural macrophage and dendritic cell counts associated with enhanced tumour cell PD-L1 expression potentially contributing to the immunosuppressive, growth-promoting microenvironment of ulcerated primary melanomas.
MeSH term(s)	Adaptive Immunity ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; B7-H1 Antigen/metabolism ; Brain Neoplasms/secondary ; CD11c Antigen/metabolism ; Dendritic Cells/metabolism ; Female ; Humans ; Immunity, Innate ; Macrophages/metabolism ; Male ; Melanoma/complications ; Melanoma/metabolism ; Melanoma/secondary ; Middle Aged ; Neoplasm Recurrence, Local/immunology ; Receptors, Cell Surface/metabolism ; Skin Neoplasms/complications ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology ; Skin Ulcer/etiology ; Skin Ulcer/immunology ; Skin Ulcer/pathology ; Tumor Microenvironment ; Young Adult
Chemical Substances	Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; B7-H1 Antigen ; CD11c Antigen ; CD163 antigen ; CD274 protein, human ; CD68 antigen, human ; Receptors, Cell Surface
Language	English
Publishing date	2018-11-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1128828-0
ISSN	1468-3083 ; 0926-9959
ISSN (online)	1468-3083
ISSN	0926-9959
DOI	10.1111/jdv.15302
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Zs.A 3492: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 413: Show issues

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Article ; Online: Sox2 is dispensable for primary melanoma and metastasis formation.

Schaefer, S M / Segalada, C / Cheng, P F / Bonalli, M / Parfejevs, V / Levesque, M P / Dummer, R / Nicolis, S K / Sommer, L

Oncogene

2017 Volume 36, Issue 31, Page(s) 4516–4524

Abstract: Tumor initiation and metastasis formation in many cancers have been associated with emergence of a gene expression program normally active in embryonic or organ-specific stem cells. In particular, the stem cell transcription factor Sox2 is not only ... ...

Abstract	Tumor initiation and metastasis formation in many cancers have been associated with emergence of a gene expression program normally active in embryonic or organ-specific stem cells. In particular, the stem cell transcription factor Sox2 is not only expressed in a variety of tumors, but is also required for their formation. Melanoma, the most aggressive skin tumor, derives from melanocytes that during development originate from neural crest stem cells. While neural crest stem cells do not express Sox2, expression of this transcription factor has been reported in melanoma. However, the role of Sox2 in melanoma is controversial. To study the requirement of Sox2 for melanoma formation, we therefore performed CRISPR-Cas9-mediated gene inactivation in human melanoma cells. In addition, we conditionally inactivated Sox2 in a genetically engineered mouse model, in which melanoma spontaneously develops in the context of an intact stroma and immune system. Surprisingly, in both models, loss of Sox2 did neither affect melanoma initiation, nor growth, nor metastasis formation. The lack of a tumorigenic role of Sox2 in melanoma might reflect a distinct stem cell program active in neural crest stem cells and during melanoma formation.
MeSH term(s)	Animals ; Humans ; Melanoma/etiology ; Melanoma/mortality ; Melanoma/secondary ; Mice ; SOXB1 Transcription Factors/physiology
Chemical Substances	SOX2 protein, human ; SOXB1 Transcription Factors ; Sox2 protein, mouse
Language	English
Publishing date	2017-04-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/onc.2017.55
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Zs.A 2218: Show issues

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Article ; Online: An exploratory study investigating the metabolic activity and local cytokine profile in patients with melanoma treated with pazopanib and paclitaxel.

Thurneysen, S / Cheng, P F / Nagel, H W / Kunz, M / Jaberg-Bentele, N / Nägeli, M / Ziegler, M / Guenova, E / Goldinger, S M / Mangana, J / Levesque, M P / Dummer, R

The British journal of dermatology

2016 Volume 175, Issue 5, Page(s) 966–978

Abstract: Background: There is a medical need for new drugs in patients with BRAF wild-type metastatic melanoma. Pazopanib is a multitarget tyrosine kinase inhibitor with antitumour and antiangiogenic activity.: Objectives: The primary aim was to investigate ... ...

Abstract	Background: There is a medical need for new drugs in patients with BRAF wild-type metastatic melanoma. Pazopanib is a multitarget tyrosine kinase inhibitor with antitumour and antiangiogenic activity. Objectives: The primary aim was to investigate the metabolic response to pazopanib monotherapy and pazopanib plus paclitaxel in patients with BRAF wild-type melanoma. Secondary end points were the early cytokine and chemokine profiles and histological findings. Methods: Pazopanib (400 mg twice daily) was administered orally from days 1 to 10 and from days 14 to 70. An intravenous infusion with paclitaxel (150 mg m Results: Two patients failed screening and 17 were dosed. Of 67 adverse events, nine (13%) were grade 3 or 4. Five of 14 evaluable patients had a partial metabolic response at day 10 under pazopanib monotherapy. The response rate at day 70 under combined pazopanib-paclitaxel treatment was 0%. Immunohistochemistry revealed an increase of M2-like macrophages in nonresponders compared with responders. We observed a significant upregulation of five cytokines (CXCL1, CXCL2, CXCL13, CCL22 and SPP1) in responding vs. nonresponding lesions. Overall, the median progression-free survival was 70 days (range 5-331), which did not differ significantly between responders (148 days) and nonresponders (70 days, P = 0·17). Conclusions: In this patient population pazopanib efficacy was limited. Response is associated with low M2-like macrophage density and increased expression of several chemokines.
MeSH term(s)	Administration, Oral ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cytokines/metabolism ; Drug Administration Schedule ; Female ; Humans ; Infusions, Intravenous ; Male ; Melanoma/drug therapy ; Melanoma/metabolism ; Paclitaxel/administration & dosage ; Pyrimidines/administration & dosage ; Skin Neoplasms/drug therapy ; Skin Neoplasms/metabolism ; Sulfonamides/administration & dosage ; Treatment Outcome ; Up-Regulation
Chemical Substances	Cytokines ; Pyrimidines ; Sulfonamides ; pazopanib (7RN5DR86CK) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2016-11
Publishing country	England
Document type	Clinical Trial ; Journal Article
ZDB-ID	80076-4
ISSN	1365-2133 ; 0007-0963
ISSN (online)	1365-2133
ISSN	0007-0963
DOI	10.1111/bjd.14727
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Ui VI Zs.23: Show issues

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Article ; Online: Basal cell carcinomas in a tertiary referral centre: a systematic analysis.

Dreier, J / Cheng, P F / Bogdan Alleman, I / Gugger, A / Hafner, J / Tschopp, A / Goldinger, S M / Levesque, M P / Dummer, R

The British journal of dermatology

2014 Volume 171, Issue 5, Page(s) 1066–1072

Abstract: Background: Basal cell carcinoma (BCC) is the most frequent skin cancer with increasing incidence and generally high cure rates. BCC can be quite aggressive and is difficult to treat.: Objectives: To investigate BCCs with a focus on histological ... ...

Abstract	Background: Basal cell carcinoma (BCC) is the most frequent skin cancer with increasing incidence and generally high cure rates. BCC can be quite aggressive and is difficult to treat. Objectives: To investigate BCCs with a focus on histological subtypes, treatment procedures and correlation to clinical progress to collect further information on complex BCC cases. Methods: In this retrospective single-centre analysis the dermatopathology database, a network of cooperating dermatological surgeons, was queried for BCC cases between January 2007 and December 2011. Of 14,423 samples from a total of 9652 patients initially identified, 2938 patients were treated at the University Hospital Zurich and had corresponding local electronic patient records. Results: Patients (n = 2938) (with 4769 diagnoses, 2006 re-excisions with 1180 microscopically controlled surgeries) were classified based on severity estimations into 2240 simple, 640 moderate, and 58 severe cases, including one BCC-treatment-associated death and 11 patients with subsequent participation in a clinical trial. In moderate and severe cases (n = 698), there were significantly higher rates of unique histological diagnoses (n = 2·5; P < 0·0001), higher association with basosquamous carcinoma [odds ratio (OR) 3·6; P < 0·0001] and sclerosing BCC (OR 2·48; P < 0·0001). Of the patients with basosquamous carcinoma 82·6% had a previous history of BCC. Conclusions: This is the first study that analyses the frequency of complicated BCCs in a tertiary referral centre. There were 6·6% moderate (640 of 9652) and 0·6% (58 of 9652) severe cases. We found significantly more varying histological diagnoses and significant association with aggressive subtypes in moderate and severe cases. These patients might especially benefit from new therapeutic options.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Carcinoma, Basal Cell/pathology ; Carcinoma, Basal Cell/surgery ; Female ; Germany ; Hospitalization ; Humans ; Male ; Middle Aged ; Mohs Surgery/statistics & numerical data ; Retrospective Studies ; Skin Neoplasms/pathology ; Skin Neoplasms/surgery ; Tertiary Care Centers
Language	English
Publishing date	2014-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80076-4
ISSN	1365-2133 ; 0007-0963
ISSN (online)	1365-2133
ISSN	0007-0963
DOI	10.1111/bjd.13217
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Ui VI Zs.23: Show issues

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Article: Retinoic acid perturbs the expression of Xhox.lab genes and alters mesodermal determination in Xenopus laevis.

Sive, H L / Cheng, P F

Genes & development

1991 Volume 5, Issue 8, Page(s) 1321–1332

Abstract: Retinoic acid (RA) treatment of Xenopus laevis embryos leads to anterior truncation of the body axis (Durston et al. 1989; Sive et al. 1990). These initial studies suggested that RA may play a role in the patterning of the primary body axis. At least one ...

Abstract	Retinoic acid (RA) treatment of Xenopus laevis embryos leads to anterior truncation of the body axis (Durston et al. 1989; Sive et al. 1990). These initial studies suggested that RA may play a role in the patterning of the primary body axis. At least one target of RA was shown previously to be dorsal ectoderm. In this report we extend this observation and also ask whether RA alters the determination and inducing capacity of mesodermal tissue. To facilitate this analysis we isolated the homeo-domain-containing genes Xhox.lab1 and Xhox.lab2. These genes were expressed in both ectoderm and mesoderm during the RA-sensitive period and were strongly induced by RA in both germ layers. In particular, anterior regions expressed low levels of Xhox.lab RNAs in untreated embryos but showed increased expression after RA application. We show further that although RA-treated embryos contained anterior-inducing mesoderm, the amount of this activity appeared to be lower than that of controls. Additionally, we document that RA suppressed lateral (muscle) and ventral (blood) mesoderm differentiation. The data indicate that RA alters mesodermal determination and causes axial perturbation both by depressing the ability of dorsal mesoderm to induce anterior structures and by altering the response of dorsal ectoderm to induction. These analyses suggest that Xhox.lab genes may be responsible, in part, for mediating the RA effect.
MeSH term(s)	Amino Acid Sequence ; Animals ; Blotting, Northern ; Ectoderm/drug effects ; Ectoderm/physiology ; Embryo, Nonmammalian/drug effects ; Embryo, Nonmammalian/physiology ; Embryo, Nonmammalian/radiation effects ; Gene Expression/drug effects ; Gene Expression/radiation effects ; Genes, Homeobox/drug effects ; Mesoderm/drug effects ; Mesoderm/physiology ; Mesoderm/radiation effects ; Molecular Sequence Data ; Multigene Family ; Plasmids ; Sequence Homology, Nucleic Acid ; Tretinoin/pharmacology ; Ultraviolet Rays ; Xenopus laevis
Chemical Substances	Tretinoin (5688UTC01R)
Language	English
Publishing date	1991-08
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.5.8.1321
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Zs.A 2292: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 54: Show issues

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Article: Use of a conditional MyoD transcription factor in studies of MyoD trans-activation and muscle determination.

Hollenberg, S M / Cheng, P F / Weintraub, H

Proceedings of the National Academy of Sciences of the United States of America

1993 Volume 90, Issue 17, Page(s) 8028–8032

Abstract: DNA sequences encoding the hormone-binding domains of several steroid hormone receptors were fused in frame to the MyoD gene. When the gene for this chimeric protein was expressed in NIH 3T3 or 10T1/2 fibroblasts, these cells displayed hormone-dependent ... ...

Abstract	DNA sequences encoding the hormone-binding domains of several steroid hormone receptors were fused in frame to the MyoD gene. When the gene for this chimeric protein was expressed in NIH 3T3 or 10T1/2 fibroblasts, these cells displayed hormone-dependent induction of myogenesis. Our experiments focused on cell lines expressing estrogen receptor-MyoD chimeras. Induction of these lines in the presence of estradiol and an inhibitor of protein synthesis, cycloheximide, resulted in the activation of the endogenous myogenin gene but did not activate the muscle-specific creatine kinase or cardiac alpha-actin gene. This result suggests that MyoD is not a "direct" activator of these downstream myogenic genes but must first activate myogenin as an intermediary. Once muscle is induced by estrogen receptor-MyoD the muscle phenotype is very stable and does not need the continued presence of estradiol for its maintenance.
MeSH term(s)	3T3 Cells ; Actins/biosynthesis ; Animals ; Base Sequence ; Cell Differentiation ; Creatine Kinase/biosynthesis ; Cycloheximide/pharmacology ; Estradiol/pharmacology ; Gene Expression Regulation ; Genetic Vectors ; Humans ; Isoenzymes ; Mice ; Molecular Sequence Data ; Muscle Proteins/biosynthesis ; Muscle Proteins/metabolism ; Muscles/cytology ; Muscles/physiology ; MyoD Protein ; Oligodeoxyribonucleotides ; Oligonucleotides, Antisense ; Polymerase Chain Reaction ; Receptors, Estrogen/biosynthesis ; Receptors, Estrogen/metabolism ; Receptors, Glucocorticoid/biosynthesis ; Receptors, Glucocorticoid/metabolism ; Receptors, Thyroid Hormone/biosynthesis ; Receptors, Thyroid Hormone/metabolism ; Recombinant Fusion Proteins/biosynthesis ; Recombinant Fusion Proteins/metabolism ; Transcription Factors/metabolism ; Transfection
Chemical Substances	Actins ; Isoenzymes ; Muscle Proteins ; MyoD Protein ; Oligodeoxyribonucleotides ; Oligonucleotides, Antisense ; Receptors, Estrogen ; Receptors, Glucocorticoid ; Receptors, Thyroid Hormone ; Recombinant Fusion Proteins ; Transcription Factors ; Estradiol (4TI98Z838E) ; Cycloheximide (98600C0908) ; Creatine Kinase (EC 2.7.3.2)
Language	English
Publishing date	1993-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.90.17.8028
Database	MEDical Literature Analysis and Retrieval System OnLINE

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